The increased availability of testing for breast cancer predisposing gene mutations (e.g. BRCA1 and BRCA2) will soon result in a major increase in the number of young women identified as mutation carriers who require early and continuous surveillance. Means for early detection of chromosomal changes in women, especially those with family history of mutations, is needed. Mammography alone may not be sufficient for such evaluation. The effectiveness of mammography has not been established in women younger than 40 years of age. Younger women have more dense breast tissue, with reduced mammographic sensitivity. Moreover, tumor growth rates are often higher in younger women, thereby necessitating more frequent screening. However, carriers of some mutations (such as ataxia telangiectasia) may have increased sensitivity to radiation and could, conceivably, be harmed by frequent mammograms. Hence, new means of evaluation which avoid exposure to radiation would be particularly appropriate for use in younger women.
Nipple aspirate fluid (NAF) is secreted continuously by the non-lactating breast and, in 50% to 70% of premenopausal women, can be aspirated through duct openings in the nipple using a simple non-invasive pump. NAF is of interest because it has a relatively long retention time in the breast alveolar-ductal system, where it accumulates exfoliated mammary epithelial cells. Thus, cytogenetic examination of cells found in NAF would provide a "snapshot" of the micro-environment where breast cancer originates.
To date, classical cytologic assessment has been used to identify abnormalities in NAF-derived cells as an indicator of early progression toward breast cancer. However, NAF cytology alone is not sufficiently sensitive to identify the subgroup of women who are on a progression pathway that will lead to breast cancer. Atypical epithelial cells destined to progress to cancer have often accumulated a number of premalignant molecular changes. These changes are sufficiently subtle to require more sensitive, refined genetic analyses for their detection. Therefore, it is important to improve the sensitivity afforded by NAF cytology by examining these cells for chromosomal abnormalities.